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CASE REPORT
Ahead of print publication  

Use of haloperidol in amiodarone induced delirium


1 Department of Psychiatry, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Psychiatry, Central Command, Lucknow, Uttar Pradesh, India

Date of Submission10-Jun-2021
Date of Decision24-Jun-2021
Date of Acceptance05-Dec-2021
Date of Web Publication01-Feb-2022

Correspondence Address:
Markanday Sharma,
Department of Psychiatry, Armed Forces Medical College, Pune - 411 040, Maharashtra
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aip.aip_72_21

  Abstract 


Amiodarone, a versatile Class III antiarrhythmic drug, is considered one of the most effective agents in counteracting supraventricular and ventricular tachyarrhythmia. Delirium related to amiodarone therapy is infrequently associated with amiodarone. Although the prevalence of this disorder is extremely low, it is worthy of note the time-dependent relationship between the onset of therapy and the beginning of psychiatric symptoms. We report the case of an older woman who was diagnosed with a case of decompensated dilated cardiomyopathy with atrial fibrillation. She developed delirium after treatment with amiodarone. It also highlights the use of antipsychotic, despite continuous use of amiodarone.

Keywords: Amiodarone, delirium, drug induced



How to cite this URL:
Sharma R, Singh R, Sharma M. Use of haloperidol in amiodarone induced delirium. Ann Indian Psychiatry [Epub ahead of print] [cited 2022 Dec 2]. Available from: https://www.anip.co.in/preprintarticle.asp?id=337022




  Introduction Top


Amiodarone is an iodinated benzofuran derivative containing about 37% of organic iodine structurally similar to thyroid hormones. Amiodarone is a Class III antiarrhythmic drug effective in counteracting supraventricular and ventricular tachyarrhythmia. Its toxicity profile involves tremor, ataxia, and peripheral neuropathy.[1] Psychiatric disturbances in the form of acute-onset amiodarone-induced delirium and depression have been reported in the literature.[2] Evidence regarding the treatment protocol of such condition is even scarce.

We are reporting the management of amiodarone-induced delirium in a case of decompensated dilated cardiomyopathy with atrial fibrillation. Our patient developed delirium characterized by disorientation to time, place, and person, abusive and combative behavior, irrelevant talk, and insomnia after the administration of amiodarone, which resolved in 7 days with the institution of haloperidol despite continuation on amiodarone. The aim of this report is to add evidence for the use of antipsychotic in the management of amiodarone-induced delirium, in case amiodarone-like antiarrhythmics are an inevitable requirement.


  Case Report Top


A 71-year-old female homemaker with no family or past history of any psychiatry or medical illness was admitted to the general female ward command hospital Pune on May 12, 2018, with complaints of heaviness of breath for the past 1 year and cough with expectoration of 7-day duration. The evaluation revealed decompensated dilated cardiomyopathy with atrial fibrillation. Initially, rhythm control was started using injection diltiazem infusion for day 1 and day 2. In view of compromised hemodynamic state and atrial tachyarrhythmia, followed by switching to loading by injection amiodarone 150 mg bolus followed by 60 mg/h for 6 h and subsequently 30 mg/h for the next 18 h on day 3 was done. On day 4 at around 1700 h, she developed sudden-onset progressive disorientation to time, place, and person, abusive and combative behavior, and irrelevant talk for which psychiatric consultation was requested. On day 5, psychiatric evaluation was suggestive of delirium, which was temporally associated with the institution of amiodarone.

In view of the absence of any other offending agent or infectious etiology and available literature favoring of evidence for amiodarone-induced to impairment of consciousness and attention, global disturbance of cognition and disturbance of the sleep-wake cycle, a diagnosis of delirium, not induced by alcohol and other psychoactive substances (F05) as per the diagnostic criteria of the International Classification of Diseases-10 (likely drug induced) was given.[3] The case was discussed with treating cardiologist, who expressed his inability to change the dosage and frequency of antiarrhythmic considering the patient's condition. In view of first-line agent and low-moderate effect on QTc, she was treated with injection haloperidol 2.5 mg IM slow 12 hourly for the next 2 days with which her symptoms reduced.[4] However, there were episodes of fluctuating sensorium. In view of long t1/2 of amiodarone and its metabolites (60 days), she was continued to oral haloperidol 2.5 mg bis in die (BD) and response to haloperidol, she was finally discharged on day 12. She was continued amiodarone therapy with advice to continue tablet haloperidol 2.5 mg BD. Her symptoms resolved completely within a week. Her antipsychotic was gradually tapered off in the next 4 weeks without any recurrence of symptoms.


  Discussion Top


Delirium is characterized by an acute decline in both the level of consciousness and cognition with particular impairment in attention. A life-threatening, yet potentially reversible disorder of the central nervous system (CNS), delirium often involves perceptual disturbances, abnormal psychomotor activity, and sleep cycle impairment. Delirium is often underrecognized by health-care workers. Delirium is a poor prognostic sign. Rates of institutionalization are increased threefold for patients 65 years and older who exhibit delirium while in the hospital. The 3-month mortality rate of patients who have an episode of delirium is estimated to be 23%–33%. The 1-year mortality rate for patients who have an episode of delirium may be as high as 50%. The major causes of delirium are CNS disease (e.g., epilepsy), systemic diseases, and either intoxication or withdrawal from pharmacological or toxic agents.[5]

Adverse effects of medications on cholinergic and dopaminergic function have been implicated in the pathophysiology of delirium. Histopathologic changes, such as the formation of lysosomal inclusion bodies in Schwann cells and demyelination have been found in sural nerve biopsies from patients with peripheral neuropathy who were treated with amiodarone, suggesting that altered lysosomal function may contribute to the presumed neurotoxic effect of the drug.[5]

Haloperidol has demonstrated pharmacologic activity at a number of receptors in the brain, it has strong antagonism of the dopamine receptor (mainly D2), particularly within the mesolimbic and mesocortical systems of the brain. The optimal clinical efficacy of antipsychotics is associated with the blockade of approximately 60%–80% of D2 receptors in the brain and thought to improve psychotic symptoms by halting this overproduction of dopamine. It acts primarily on the D2-receptors and has some effect on 5-HT2 and α1-receptors, with negligible effects on dopamine D1-receptors. The drug also exerts some blockade of α-adrenergic receptors of the autonomic system. It eliminating dopamine neurotransmission and leading to the reduction in perceptual disturbances, altered sleep-wake cycle, and agitation that are commonly associated with delirium.[6]

Amiodarone is a Class III antiarrhythmic drug with noncompetitive α-and β-adrenergic inhibitory effects that prolong the myocardial cell action potential and refractory period.[7] The drug is metabolized to desethylamiodarone by the cytochrome P450 (CYP) enzymes CYP3A4 and CYP2C8. Amiodarone has a long half-life (~58 days), and drug clearance is reduced in adults ≥65 years of age. Amiodarone was not associated with an increased incidence of delirium following cardiac surgery when the drug was used in controlled trials to prevent postoperative atrial fibrillation. Amiodarone and its active metabolite cross the blood–brain barrier, and concentrations of the parent drug and metabolite have been measured in the CNS.[8] The Naranjo Adverse Drug Reaction Probability Scale[9] of this case scored 7 (probable adverse drug reaction). Nonpsychiatric, central and peripheral nervous system adverse effects (primarily tremor, ataxia, and peripheral neuropathy) have been associated with amiodarone, and considerable variability has been observed in the time to onset and resolution of drug-related symptoms.[10] In our case, unusual features were rapid onset of delirium, and resolution of her symptoms was within a similar time frame. This variability may be explained by the drug's large volume of distribution and its elimination half-life of 26–100 days. Principle of management includes removal of deliriogenic medications, analgesia, use of low-dose atypical or typical antipsychotics, and nonpharmacological interventions. This case reports highlighting the use of haloperidol, despite continuous use of amiodarone-like drug, and hypothesize that antipsychotic might have an indirect role in bringing down the severity of delirium due to the use of amiodarone through an indirect mechanism apart from its use in acute behavioral control.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Goldschlager N, Epstein AE, Naccarelli GV, Olshansky B, Singh B, Collard HR, et al. A practical guide for clinicians who treat patients with amiodarone: 2007. Heart Rhythm 2007;4:1250-9.  Back to cited text no. 1
    
2.
Salouage I, Klouz A, Trabelsi S, Zaïem A, Gaïes E, Loueslati MH, et al. Neuro-psychiatric disorders induced by amiodarone high levels (Cordarone®). Therapie 2007;62:357-9.  Back to cited text no. 2
    
3.
Organization WH. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva: World Health Organization; 1992. Available from: https://apps.who.int/iris/handle/10665/37958. [Last accessed on 2021 Jun 24].  Back to cited text no. 3
    
4.
Schrijver EJ, de Vries OJ, van de Ven PM, Bet PM, Kamper AM, Diepeveen SH, et al. Haloperidol versus placebo for delirium prevention in acutely hospitalised older at risk patients: A multi-centre double-blind randomised controlled clinical trial. Age Ageing 2018;47:48-55.  Back to cited text no. 4
    
5.
Sadock, Benjamin J, Sadock V, Ruiz P. Kaplan and Sadock's Comprehensive Textbook of Psychiatry. 10th ed. Wolters Kluwer; 2017.  Back to cited text no. 5
    
6.
Shen YZ, Peng K, Zhang J, Meng XW, Ji FH. Effects of haloperidol on delirium in adult patients: A systematic review and meta-analysis. Med Princ Pract 2018;27:250-9.  Back to cited text no. 6
    
7.
Colunga Biancatelli RM, Congedo V, Calvosa L, Ciacciarelli M, Polidoro A, Iuliano L. Adverse reactions of amiodarone. J Geriatr Cardiol 2019;16:552-66.  Back to cited text no. 7
    
8.
Foley KT, Bugg KS. Separate episodes of delirium associated with levetiracetam and amiodarone treatment in an elderly woman. Am J Geriatr Pharmacother 2010;8:170-4.  Back to cited text no. 8
    
9.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 9
    
10.
Orr CF, Ahlskog JE. Frequency, characteristics, and risk factors for amiodarone neurotoxicity. Arch Neurol 2009;66:865-9.  Back to cited text no. 10
    




 

 
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